tbuckley/cabot-search huggingface dataset:
Clinicopathological characteristics and survival outcomes for testicular choriocarcinoma and non-testicular choriocarcinoma: A SEER database analysis.
Authors: Sakhr Abdulsalam Alshwayyat, Obada Ehab Ababneh, Tala Abdulsalam Alshwayyat, Marwa Thaker Qaddoura, Maen Suliman Soudi
Journal: Journal of Clinical Oncology (2023)

e17026 Background: Primary Choriocarcinoma (CC) is a rare germ cell tumor that can occur in males. The most common primary site in men is the testis. It can occur in extragonadal sites such as the mediastinum, retroperitoneum, lungs or brain. The clinical and prognostic differences between testicular CC and non-testicular CC are unclear. We aim to study the differences in clinical features, prognostic factors, and outcomes between the two subtypes of CC. Methods: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with pure CC between 2000 and 2018. Patients with a previous history of cancer or with other concurrent malignancies were excluded. These patients were divided into two groups: testicular and non-testicular CC. The clinicopathological features of each group were compared using chi-square tests. Kaplan-Meier estimator, log-rank tests, and Cox proportional hazard regression were used to identify prognostic factors over overall survival (OS) and cancer-specific survival (CSS). Results: The study included 363 patients, with 270 (74.4%) patients classified as having testicular CC and 93 (25.6%) as having non-testicular CC. The results showed that testicular CC was more likely to occur in white patients, be bilateral in distribution, have a smaller size, and be in more advanced SEER stages compared to non-testicular CC. Additionally, testicular CC patients were more likely to undergo surgical treatment, but not radiation. Testicular CC patients had a better OS and CSS (HR = 0.52, 95% CI: 0.38-0.71 and HR = 0.52, 95% CI: 0.37-0.71, respectively) compared with non-testicular CC. Our Cox multivariate analyses for OS and CSS identified the following independent prognostic factors for testicular CC: localized stage, surgery, tumor size ≥ 4cm, radiotherapy, and chemotherapy. Interestingly, the use of radiotherapy was actually associated with poor OS and CSS (HR = 1.8, 95% CI: 1.17-2.85 and HR = 1.7, 95% CI: 1.05-2.73, respectively). For non-testicular CC, the independent prognostic factors for OS and CSS were age ≥ 30 years, non-paired site, regional stage, surgery, and chemotherapy. Conclusions: Our study provides important insights into the differences between testicular and non-testicular CC. The use of radiotherapy is generally not recommended in testicular CC which might explain its bad prognostic effect as these patients might be naturally at higher risk of dying. However, the bad poor prognosis of patients using radiotherapy persisted even after controlling for other important prognostic factors. Further studies with larger sample sizes are needed to validate and build upon these findings, but our results provide a starting point for a better understanding of such rare cancer.
Immunoglobulin as a predictive biomarker for the efficacy of immune checkpoint inhibitor combined with VEGF-TKI in metastatic renal cell carcinoma.
Authors: Honglei Cui, Jie Wu, Wang Qu, Linjun Hu, Ai-Ping Zhou, Jian-Zhong Shou
Journal: Journal of Clinical Oncology (2023)

4543 Background: The combination of immune checkpoint inhibitor (ICI) and vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI) is recommended as the first-line treatment in patients with metastatic clear cell renal cell carcinoma (ccRCC). However, no effective serum biomarker has been used to predict the therapy response and potential benefits. Abnormal content and changes of immunoglobulin (IG) in serum or cancer tissue may indicate cancer progression and impact the prognosis. We examined the content of serum IG and analyzed the alteration after treatment to assess the efficacy of ICI and VEGF-TKI. Methods: Eighty-four patients with metastatic ccRCC were enrolled in this study. The total serum IG level was determined as the sum of IgA, IgG, and IgM. The data of baseline level and alteration of IG after 3-mo treatment was complete in 72 ccRCC patients. These patients were then divided into two groups based on alteration in their IG levels: the IG-increased group and the IG-decreased group. This study aimed to investigate the correlation between the baseline level of immunoglobulin (IG), changes in its content after 3-mo of treatment, and clinical outcomes. Results: Eighty-four patients were retrospectively enrolled with a median follow-up of 17.3 months (2.5-45.1). The objective response rate (ORR) was 41.67%, and the median overall survival (OS) was 31 months in our cohort. The baseline level of IG was not associated with ORR or OS. However, dynamic alteration in IG level after 3-mo treatment had a significant impact on ORR and OS in ccRCC patients. The ORR was 2.7% in the IG-increased group and 80.0% in the IG-decreased group. The OS was 21.0 months (95% CI 14.0–NA) in the IG-increased group and 48.0 months (28·0–NA) in the IG decreased-group (Hazard ratio [HR] 4.59, p=0·003). Conclusions: The change of serum IG level after 3-mo treatment served as an effective predictor of drug response and the prognosis for metastatic ccRCC patients. Value of serum IG needs to be validated in multi-centers and the mechanism of it should be further investigated.
[<sup>18</sup>F]FDG-PET to identify pathological responses upon neoadjuvant immune checkpoint blockade in cutaneous squamous cell carcinoma.
Authors: Sabine Breukers, Robert D. Crommelin, Laura Smit, J.P. De Boer, Arash Navran, Winan J. van Houdt, Remco de Bree, Lot A. Devriese, John B. A. G. Haanen, Charlotte L. Zuur, Maurits Wondergem
Journal: Journal of Clinical Oncology (2023)

9584 Background: To improve clinical prospects of patients with locally advanced cutaneous SCC (CSCC), we tested the efficacy of neoadjuvant nivolumab with or without ipilimumab prior to standard of care curative surgery ± radiotherapy; the MATISSE trial (NCT04620200). Neoadjuvant immunotherapy-response prediction via FDG-PET imaging was demonstrated feasible in the IMCISION trial (PMID 34937871), where a decrease of ≥12.5% in total-lesion glycolysis (TLG) upon immunotherapy identified deep pathological responders to immunotherapy in head and neck SCC prior to surgery with 95% accuracy. The current research investigates the predictive power of FDG-PET to identify deep pathological responses to neoadjuvant immunotherapy in MATISSE patients. Methods: 26 patients with primary CSCC (stage I‒IVa) were treated with neoadjuvant nivolumab with (n = 14) or without (n = 12) ipilimumab (weeks 0 and 2). FDG-PET/CT scans were evaluable at baseline and shortly before surgery (week 4) in 20 patients. Images were analysed for SUV max , metabolic tumor volume (MTV), and TLG. Responders to immunotherapy were defined as having a major or partial pathological response to immunotherapy (MPR and PPR, showing ≤ 10% and 11-50% remaining viable cancer cells at time of surgery, respectively). Results: Overall, median SUV max , MTV, and TLG decreased upon immunotherapy at the primary tumor site in responders (n = 15),whereas median SUV max , MTV and TLG increased in non-responders (Table). Three patients with stable or increased SUV max , MTV and TLG, also showed a pathological response and were classified as pseudo-progressive. Another patient with a MPR had an increase in SUV max , but a decrease in MTV and TLG. All patients with any decline in SUV max , MTV or TLG at the primary tumor site showed a pathological response (PPV 100%) and none of them developed a relapse at median follow-up 9.0 months. Conclusions: Primary tumor response assessment using FDG-PET-based ΔSUVmax, ΔMTV and ΔTLG accurately identifies pathological responses early upon neoadjuvant immunotherapy in cutaneous SCC. FDG-PET could, upon validation, select CSCC patients for response-driven treatment adaptation in future trials. FDG-PET-CT upon neoadjuvant immunotherapy in CSCC, changes in PET-parameters and predictive values of any decline in SUV max , MTV or TLG. Clinical trial information: NCT04620200 . [Table: see text]
Awareness of testicular cancer and testicular self-examination in young adults, and the efficacy of education-based media.
Authors: Aaron M. Walt, Micah Levy, Chih Peng Chin, Bobby Chi-Hung Liaw, Michael Palese
Journal: Journal of Clinical Oncology (2023)

e17022 Background: The prevalence of testicular cancer in adolescents and young adults creates a unique opportunity for education through social media. We investigated this populations’ baseline knowledge of testicular cancer (TC) and testicular self-examination (TSE) and identified the efficacy of various forms of media in educating young individuals. Methods: A survey was designed to assess participants’ baseline knowledge of TC and TSE. Participants were randomly shown one of three forms of educational media created by the Testicular Cancer Society and the National Cancer Institute. These were an infographic, a short (60 second) and a long (6 minute) video. Participants were then asked to correctly identify facts regarding TC and TSE. Baseline knowledge was analyzed by age (&lt; 24 vs. &gt; 25), and post-media knowledge was analyzed to determine the efficacy of each media form. Results: Responses from 328 participants were analyzed, with a mean age of 24.3 years, 40.9% male, 72.0% white, and 70.7% graduated college or a graduate program. Only 30.7% of participants reported being educated about TC, 25.9% correctly identified the 15-35 age group as having the highest prevalence of TC, and 26.3% correctly identified the TC survival rate as being 75-100%. The &gt; 25-year-old group were significantly more likely to have heard of TSE (p &lt; 0.001), performed a TSE if male (p = 0.043), encouraged males to perform TSE if female (p &lt; 0.001) and correctly identify TC survival rate (p = 0.006) and treatability (p = 0.007). Long video viewers were significantly less likely to watch it in its entirety compared to infographic and short video viewers, and they were less likely to report an understanding of TSE compared to infographic viewers. Short video viewers were less likely to have properly identified the TC survival rate compared to both infographic (P &lt; 0.001) and long video viewers (p = 0.001). Conclusions: Overall there is poor awareness and education regarding TC and TSE, with adolescents performing significantly worse than young adults. The infographic performed the best overall in completion and education about TC and TSE, with the short video performing similarly well, and the long video performing the worst. This suggests that easily dispersed and viewable forms of media may be the most effective tool for educating young people.[Table: see text]
Total and anatomically contextualized quantitative <sup>18</sup>F-DCFPyL PET at biochemical recurrence to predict subsequent biochemical progression free survival in patients with prostate cancer.
Authors: Hong Song, Karl Sjöstrand, Heying Duan, Valentina Ferri, Carina Mari Aparici, Guido Davidzon, Benjamin Lewis Franc, Farshad Moradi, Aseem Anand, Andrei Iagaru
Journal: Journal of Clinical Oncology (2023)

e17015 Background: PSMA PET has been widely adopted in restaging of prostate cancer at biochemical recurrence. We assess the clinical utility of quantitative parameters on 18 F-DCFPyL PET/CT at biochemical recurrence and their association with the subsequent biochemical progression free survival (bPFS). Methods: This is a retrospective image analysis and longitudinal follow up of a prospective study evaluating 18 F-DCFPyL PET in prostate cancer patients with biochemical recurrence after primary definitive treatment at Stanford Hospital. The 18 F-DCFPyL PET images were quantitatively analyzed automatically by the aPROMISE application, a semi-automated analysis and structured reporting of PSMA PET/CT. aPROMISE uses deep learning to segment detailed anatomical information from the CT images and uses this information in combination with the PET image to detect and quantify candidates for prostate cancer lesions. The reader works in tandem with the software to vet the final list of lesions, from which the quantitative assessments and final report is created automatically. Based on the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria. SUVmean, PSMA positive total tumor volume (PSMAttv) and aPSMA scores, a quantitative score for tumor burden measuring the interaction of tumor volume and uptake stratified by local tumors (aPSMA-miT), regional lymph nodes (aPSMA-miN) and distant metastases (aPSMA-miMa for extrapelvic metastases, miMb for bone metastases and miMc for other organ metastases) were obtained based on the miTNM classification. The association of these quantitative parameters with the subsequent bPFS was evaluated. Results: 134 patients (age 70.1 ± 7.6, range 51 -91 years; PSA 13.9 ± 98.5, range 0.12 – 1126 ng/mL) were included in the quantitative image analysis. aPROMISE detected nodal and/or bone metastases in 94 of 134 patients (70%) and only 12 of 134 patients (9%) had visceral disease. With median follow up of 37 months, 66 of 134 patients (49%) have progressed again biochemically after treatment. The bPSF was 25.8 ± 15.1 months. Quantitative analysis of 18 F-DCFPyL PET found that the subsequent bPFS is significantly associated with aPSMA-miMb ( P &lt; 0.001), PSMAttv ( P &lt; 0.001), aPSMA-miN ( P &lt; 0.01), aPSMA-miMa ( P &lt; 0.05) but not with SUVmean or aPSMA-miMc. Conclusions: Total and anatomically contextualized quantitative image analysis of 18 F-DCFPyL PET/CT at biochemical recurrence may be useful in predicting the subsequent bPFS. Studies in larger patient cohort is necessary to validate these findings. Given many patients were treated based on lesions found on 18 F-DCFPyL PET/CT, clinical implication of this findings remains to be elucidated.
The spectrum of <i>RAF1</i> fusion positive solid tumors in children and young adults.
Authors: Jiani Chen, Jinhua Wu, Jeff Schubert, Fumin Lin, Elizabeth H. Denenberg, Alison Muir, Edward J. Romasko, Elizabeth A. Fanning, Tricia R. Bhatti, Kristina Ann Cole, Portia A. Kreiger, Peter Mattei, Minjie Luo, Yiming Zhong, Adam C Resnick, Phillip B Storm, Mariarita Santi, Lea F. Surrey, Marilyn M. Li
Journal: Journal of Clinical Oncology (2023)

e22013 Background: The RAF1 gene encodes a kinase protein in the MAPK signaling pathway. Fusions involving RAF1 have been reported in solid tumors with a higher prevalence in melanoma, breast cancer, non-small cell lung cancer, and brain tumors. The fusions typically replace the N-terminal autoinhibitory domain with the 5’ partner genes leading to autonomous activation of RAF1 kinase. The efficacy of MEK inhibitors as a potential treatment for RAF1 fusion positive tumors is under investigation. Here we present a cohort of 8 RAF1 fusions involved in a spectrum of tumors in children and young adults. Methods: A retrospective search for tumors harboring RAF1 fusion was performed using our clinical database from 2016 to date. The RNA fusion analysis targets &gt;700 exons of 117 genes for known and novel fusions. Additional genomic alterations, tumor type, and patient demographics were also collected. Results: A total of 8 cases positive for RAF1 fusion were identified from 2526 solid tumors including 6 brain tumors, 1 sarcoma, and 1 hepatoblastoma. Histologic diagnoses of the brain tumors were mostly low grade gliomas with no other driver mutations. Two pilocytic astrocytomas harbored RAF1 fusions without the pathognomonic KIAA1549: BRAF fusions. Although RAF1 fusions have been reported in rhabdomyosarcomas, it is the first time that a RAF1 fusion is associated with hepatoblastoma. 4 of the 8 RAF1 fusions identified are novel (noted with * in the table). The break points in RAF1 were at exon 7, 8, or 10, demonstrating the retention of the kinase domain. Conclusions: We report 8 RAF1 fusion positive solid tumors in children and young adults, mainly in low-grade gliomas. Although rare, the presence of a RAF1 fusion not only facilitates the tumor diagnosis but also provides genomic evidence for potential targeted therapies. References: 1. The AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discovery. 2017;7(8):818-831. 2. McEvoy CR et al. Profound MEK inhibitor response in a cutaneous melanoma harboring a GOLGA4-RAF1 fusion. J Clin Invest. 2019; 129:1940-1945. [Table: see text]
Association between the primary site of disease and the stage at diagnosis for merkel cell carcinoma: A population-based analysis.
Authors: Rajvi Gor, Pranav Gwalani, Dhairya Gor, Charan Thej Reddy Vegivinti, Twinkle Gwalani, Hiba Narvel, Anurag Adhikari, Shweta Deshpande, Yutika Dongre, Tejo Niharika Musunuru
Journal: Journal of Clinical Oncology (2023)

e21600 Background: Merkel cell carcinoma [MCC] is a rare, aggressive skin cancer with a high rate of recurrence, metastasis, and poor prognosis. It commonly involves the head and neck (HN) region (41% of diagnosed cases), followed by the upper and lower extremities and trunk in decreasing frequency. We used the Survival, Epidemiology, and End Results [SEER] November 2021 database to assess the incidence, cause-specific survival, and the association between the primary site of disease and the stage at diagnosis for primary MCC. Methods: Using the SEER-November 2021 (17 registry) database, a retrospective analysis was performed on the 4120 cases of pathologically confirmed MCC (ICD-O-3 code 8247), diagnosed between 2004-2015. Baseline characteristics were assessed using the Chi-squared test and the Kruskal-Wallis test. Multivariate multinomial logistic regression was performed to evaluate the association, with alpha at 0.05. Analysis was performed using SEERStat and SAS 9.4. Results: The overall age-adjusted incidence rate (IR) of MCC was 0.4 cases per 100,000 with an observed 5-year survival [OS] of 47.8% and cause-specific 5-year survival [CSS] of 68.7%. The median age at diagnosis was 79 years (interquartile range - 66,83) with a male preponderance (60.4%). At baseline, males had higher odds of being diagnosed at stages III or IV (p &lt; 0.001). The odds of being diagnosed at stages II, III, or IV were significantly higher in patients with the trunk as the primary site compared to the HN region with an OR 3.8 (p &lt; 0.001), 2.4 (p &lt; 0.001), and 2.2 (p = 0.001), respectively. For patients with the upper limb as the primary site, the odds of being diagnosed at stage II were 1.4 times higher than the HN region (p = 0.0095), and stage IV was 0.4 times (p = 0.03) higher. For the lower limb and hip, the odds of being diagnosed at stages II, III, or IV were significantly higher than the HN region with an OR 2.6 (p &lt; 0.001), 1.6 (p &lt; 0.0005), and 1.5 (p = 0.04), respectively. Conclusions: While less prevalent than the MCC of the HN region, patients with MCC of the trunk, upper or lower extremities had a higher probability of being diagnosed with an advanced-stage malignancy compared to the former. Additional prospective studies are required to investigate this association further and explore its significance in site-specific treatment approaches and survival factors. [Table: see text]
Evaluating the use of circulating tumor DNA (ctDNA) in patients with urothelial cancer in the context of FGFR-targeted therapy.
Authors: Elena Schönlau, David Christian Müller, Gillian Vandekerkhove, Andrew Murtha, Jack V.W. Bacon, Connor Wells, Kimia Rostin, Sunil Parimi, Krista Noonan, Naveen S. Basappa, Jenny J. Ko, Daygen L. Finch, Nimira S. Alimohamed, Tarek A. Bismar, Lucia Nappi, Matti Annala, Cecily Q. Bernales, Kim N. Chi, Alexander William Wyatt, Bernhard J. Eigl
Journal: Journal of Clinical Oncology (2023)

4577 Background: Fibroblast growth factor receptor (FGFR) inhibitors (e.g., erdafitinib) are increasingly important in the management of FGFR-mutated urothelial carcinoma. FDA-approved archival tissue testing for specific FGFR alterations was implemented as a companion diagnostic for erdafitinib. However, longitudinal sequencing studies indicate variable tumor FGFR status over time, and erdafitinib resistance mechanisms in metastatic urothelial carcinoma (mUC) are underreported. This ongoing study aims to evaluate the accuracy of cell-free DNA (cfDNA) compared to archival tissue testing in mUC for FGFR alterations detection, and to evaluate genomic mechanisms of erdafitinib resistance in cfDNA at progression. Methods: Patients with progressing mUC who were undergoing archival tissue testing for FGFR1-3 mutations and/or fusions and who had blood samples drawn during the management of their metastatic disease were eligible. Plasma cfDNA and matched leukocyte DNA were subjected to deep targeted sequencing with a custom panel including UC-specific gene loci and all clinically approved hotspots in FGFR1+2 and all exons and introns of FGFR3. Results: As of January 2023, 109 patients from 6 sites were enrolled. Median age at diagnosis was 71, 33% had upper urinary tract primaries, and 76% were male. Tissue and cfDNA results for comparison were available for 69 patients to date. Actionable somatic FGFR alterations were found in the tissue of 15 patients (31%); the most common alteration was the FGFR3 p.S249C mutation (67%). 50 of the analyzed cfDNA samples had detectable somatic circulating tumor DNA (ctDNA) variant allele fraction of 0.5% (72%). Of those, 49 had an evaluable tissue test result. Analysis of this subset revealed high concordance (92%) between the two test methods. With the assumption that archival tissue testing is considered the ‘gold standard’, sensitivity is 93% and specificity is 91%. The four discordant results comprised one cfDNA test with undetectable FGFR3-TACC3 fusion, which was detected in tissue and three positive ctDNA test results in patients with FGFR wild-type tissue tests. In one case at erdafitinib progression, ctDNA revealed multiple subclonal populations with distinct FGFR3 gatekeeper mutations suggesting polyclonal resistance. Conclusions: This ongoing study suggests cfDNA is a valuable minimally invasive adjunct to tissue-based assays for the detection of FGFR alterations to identify patients for FGFR inhibitor therapy and to monitor for mechanisms of resistance.